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Modulating the pro-apoptotic activity of cytochrome c at a biomimetic electrified interface

Abstract : Programmed cell death via apoptosis is a natural defence against excessive cell division, crucial for fetal development to maintenance of homeostasis and elimination of precancerous and senescent cells. Here, we demonstrate an electrified liquid biointerface that replicates the molecular machinery of the inner mitochondrial membrane at the onset of apoptosis. By mimicking in vivo cytochrome c (Cyt c) interactions with cell membranes, our platform allows us to modulate the conformational plasticity of the protein by simply varying the electrochemical environment at an aqueous-organic interface. We observe interfacial electron transfer between an organic electron donor decamethylferrocene and O 2 , electrocatalyzed by Cyt c. This interfacial reaction requires partial Cyt c unfolding, mimicking Cyt c in vivo peroxidase activity. As proof of concept, we use our electrified liquid biointerface to identify drug molecules, such as bifonazole, that can potentially down-regulate Cyt c and protect against uncontrolled neuronal cell death in neurodegenerative disorders.
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https://hal.univ-lorraine.fr/hal-03423494
Contributor : Grégoire Herzog Connect in order to contact the contributor
Submitted on : Wednesday, November 10, 2021 - 10:20:50 AM
Last modification on : Monday, November 15, 2021 - 1:10:06 PM

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Alonso Gamero-Quijano, Shayon Bhattacharya, Pierre-André Cazade, Andrés Molina-Osorio, Cillian Beecher, et al.. Modulating the pro-apoptotic activity of cytochrome c at a biomimetic electrified interface. Science Advances, American Association for the Advancement of Science, 2021, 7 (45), ⟨10.1126/sciadv.abg4119⟩. ⟨hal-03423494⟩

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